Ann Med. 2024 Dec;56(1):2358183. doi: 10.1080/07853890.2024.2358183. Epub 2024 May 30.

Jacob E Ollech ¹, Hagar Eran-Banai ¹, Idan Goren ², Tali Sharar Fischler ¹, Irit Avni-Biron ¹, Yifat Snir ¹, Yelena Broitman ¹, Shaked Cohen ¹, Adi Friedenberg ¹, Maor H Pauker ¹, Iris Dotan ¹, Henit Yanai ¹

Author information

¹Division of Gastroenterology, Rabin Medical Center, Petah-Tikva, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

²Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, OH, U.S.A.

Abstract

Introduction: Real-world data on tofacitinib's effectiveness is limited and mainly retrospective or registry-based. We elected to conduct a pragmatic prospective study to assess the efficacy of tofacitinib for moderate to severe ulcerative colitis (UC), aiming to evaluate the ability of intestinal ultrasound (IUS) to discriminate responders vs. non-responders in real-time.

Methods: This pragmatic prospective clinical study included consecutive adult patients starting tofacitinib treatment for active moderate to severe UC. Patients were evaluated at baseline and after 8 weeks of tofacitinib (clinical, biomarker, endoscopy, and IUS). The primary outcome was clinical response defined by a decrease in the full Mayo score (fMS) of ≥3 at week 8. Next, we explored ultrasonographic parameters in the sigmoid colon as potential real-time classifiers to differentiate between responders and non-responders at week 8.

Results: Overall, 30 adult patients started tofacitinib; the median age was 26.3 years (IQR 22.5-39.8), and 50% were female. Most patients (86.6%) had left-sided or extensive colitis, 96.7% had previously failed biologic therapy, and 60% (18/30) were on oral corticosteroids at the start of tofacitinib. At week 8, clinical response (a decrease in the fMS ≥ 3) and remission (fMS ≤ 2) rates were 40% (12/30) and 20% (6/30), respectively. Biomarker response (FC < 250µg/g) and biomarker normalization (FC ≤ 100µg/g) were achieved in 47.6% (10/21) and 38.1% (8/21) of patients, respectively. Endoscopic healing (endoscopic Mayo sub-score [EMS] ≤ 1) was achieved in 33.3% (10/30) of patients. Sigmoid bowel wall normalization as assessed by IUS (sBWT ≤ 3) was achieved in 18.2% (4/22). The best sBWT cut-off at week 8 to accurately classify endoscopic healing vs. no healing was a sBWT of 3.6 mm (AUC of 0.952 [95% CI: 0.868-1.036], p < 0.001).

Conclusion: In this real-world pragmatic prospective study, tofacitinib was an effective treatment for moderate to severe UC, and IUS at week 8 accurately discriminated treatment response from non-response.